Mice born with Combined Lipase Deficiency develop massive hyperchylomicronemia (hyperlipemia) and die within 3 days if allowed to suckle. This condition is caused by a recessive mutation, cld, in the T/t complex of chromosome 17 in mice. We found lipoprotein lipase activity was 95% below normal in heart, diaphragm muscle, brown adipose tissue and lung of cld/cld mice, and hepatic lipase activity was equally low in liver. We found unexpectedly that lipoprotein lipase activity in liver of one day old cld/cld mice at a level 40% of that in liver of unaffected litter mates. Heparin injection caused release of subnornal amounts of lipoprotein lipase activity to plasma in cld/cld mice, and had no effect on level of hepatic lipase activity in plasma of either defective or unaffected mice. Lipoprotein lipase and hepatic lipase are necessary for clearance of chylomicrons and VLDL from the blood stream. Studies of chylomicrons from cld/cld mice incubated with purified bovine milk lipoprotein lipase showed that triacylglycerol of these chylomicrons can be readily hydrolyzed by lipoprotein lipase. Thus, hyperchylomicronemia in these animals can be attributed to the very low levels of lipoprotein lipase activity in their tissues. We reported last year that tissues of cld/cld mice synthesize lipoprotein lipase protein, but it lacks catalytic activity. The possibility that a defect in glycosylation could account for lack of lipoprotein lipase activity in tissues of cld/cld mice is being studied. Lingual lipase and pancreatic lipase, which are involved in digestion of dietary fat, were assayed in tissues of cld/cld mice. Lingual lipase activity in tongue of defective mice was about ane-half of that in unaffected mice, whereas pancreatic lipase activity in pancreas of cld/cld mice was normal. Further studies will be made to determine if synthesis of lingual lipase is also impaired in cld/cld mice.